Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Glioblastoma | Primary research

Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies

Authors: Bingxian Bian, Li Li, Junyao Yang, Yi Liu, Guohua Xie, Yingxia Zheng, Liang Zeng, Junxiang Zeng, Lisong Shen

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Serum/plasma YKL-40 can be a useful index that is associated with tumor development. However, the prognostic value of serum/plasma YKL-40 in patients with solid tumors is still unclear. We aimed to utilize the existing literature to investigate the prognostic value of serum/plasma YKL-40 in solid tumors.

Methods

An extensive literature search for relevant studies was conducted with the Embase, Medline and Web of Science databases. The effect on survival was measured with the hazard ratio (HR). Then, pooled HRs and 95% confidence intervals (CIs) were calculated using the random and fixed-effects models according to the heterogeneity of the included studies.

Results

This meta-analysis was based on 41 publications and comprised a total of 7762 patients with solid tumors. The pooled HR showed that elevated serum/plasma YKL-40 was significantly associated with poor OS (HR, 1.44; 95% CI 1.33–1.56). We also found that elevated serum/plasma YKL-40 had significant prognostic effects on OS in various cancer subgroups such as gastrointestinal tumors (HR, 1.37; 95% CI 1.18–1.58), ovarian cancer (HR, 2.27; 95% CI 1.69–3.06), melanoma (HR, 1.77; 95% CI 1.18–2.67), lung cancer (HR, 1.73; 95% CI 1.35–2.23), urologic neoplasms (HR, 1.61; 95% CI 1.08–2.40) and glioblastoma (HR, 1.23; 95% CI 1.07–1.42); in contrast, the prognostic effect of serum/plasma YKL-40 was not statistically significant in breast cancer (HR, 1.07; 95% CI 0.98–1.17).

Conclusions

The available evidence supports the hypothesis that elevated serum/plasma YKL-40 is associated with poor survival in patients with solid tumors and that serum/plasma YKL-40 may serve as a novel prognostic biomarker.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
2.
Hakala BE, White C, Recklies AD. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem. 1993;268(34):25803–10.PubMed
3.
Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, et al. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J Exp Med. 2009;206(5):1149–66.PubMedPubMedCentralCrossRef
4.
Kawada M, Seno H, Kanda K, Nakanishi Y, Akitake R, Komekado H, et al. Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer. Oncogene. 2012;31(26):3111–23.PubMedCrossRef
5.
Ku BM, Lee YK, Ryu J, Jeong JY, Choi J, Eun KM, et al. CHI3L1(YKL-40) is expressed in human gliomas and regulates the invasion, growth and survival of glioma cells. Int J Cancer. 2011;128(6):1316–26.PubMedCrossRef
6.
Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang MJ, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol. 2011;73:479–501.PubMedCrossRef
7.
Faibish M, Francescone R, Bentley B, Yan W, Shao R. A YKL-40-neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers. Mol Cancer Ther. 2011;10(5):742–51.PubMedPubMedCentralCrossRef
8.
Shao R, Francescone R, Ngernyuang N, Bentley B, Taylor SL, Moral L, et al. Anti-YKL-40 antibody and ionizing irradiation synergistically inhibit tumor vascularization and malignancy in glioblastoma. Carcinogenesis. 2014;35(2):373–82.PubMedCrossRef
9.
Johansen JS, Cintin C, Jørgensen M, Kamby C, Price PA. Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer. Eur J Cancer. 1995;31A(9):1437–42.PubMedCrossRef
10.
Qin G, Li X, Chen Z, Liao G, Su Y, Chen Y, et al. Prognostic value of YKL-40 in patients with glioblastoma: a systematic review and meta-analysis. Mol Neurobiol. 2017;54(5):3264–70.PubMedCrossRef
11.
Wan G, Xiang L, Sun X, Wang X, Li H, Ge W, et al. Elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients. Oncotarget. 2017;8(3):5382–91.PubMed
12.
Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.PubMedCrossRef
13.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMed
14.
15.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.PubMedCrossRef
16.
17.
Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.PubMedCrossRef
18.
19.
Dehn H, Høgdall EV, Johansen JS, Jørgensen M, Price PA, Engelholm SA, et al. Plasma YKL-40, as a prognostic tumor marker in recurrent ovarian cancer. Acta Obstet Gynecol Scand. 2003;82(3):287–93.PubMedCrossRef
20.
Høgdall EV, Johansen JS, Kjaer SK, Price PA, Christensen L, Blaakaer J, et al. High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival. Oncol Rep. 2003;10(5):1535–8.PubMed
21.
Jensen BV, Johansen JS, Price PA. High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Clin Cancer Res. 2003;9(12):4423–34.PubMed
22.
Johansen JS, Christensen IJ, Riisbro R, Greenall M, Han C, Price PA, et al. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival. Breast Cancer Res Treat. 2003;80(1):15–21.PubMedCrossRef
23.
Johansen JS, Drivsholm L, Price PA, Christensen IJ. High serum YKL-40 level in patients with small cell lung cancer is related to early death. Lung Cancer. 2004;46(3):333–40.PubMedCrossRef
24.
Brasso K, Christensen IJ, Johansen JS, Teisner B, Garnero P, Price PA, et al. Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006;66(5):503–13.PubMedCrossRef
25.
Schmidt H, Johansen JS, Sjoegren P, Christensen IJ, Sorensen BS, Fode K, et al. Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma. J Clin Oncol. 2006;24(5):798–804.PubMedCrossRef
26.
Schmidt H, Johansen JS, Gehl J, Geertsen PF, Fode K, von der Maase H. Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma. Cancer. 2006;106(5):1130–9.PubMedCrossRef
27.
Johansen JS, Brasso K, Iversen P, Teisner B, Garnero P, Price PA, et al. Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival. Clin Cancer Res. 2007;13(11):3244–9.PubMedCrossRef
28.
Roslind A, Johansen JS, Christensen IJ, Kiss K, Balslev E, Nielsen DL, et al. High serum levels of YKL-40 in patients with squamous cell carcinoma of the head and neck are associated with short survival. Int J Cancer. 2008;122(4):857–63.PubMedCrossRef
29.
Yamac D, Ozturk B, Coskun U, Tekin E, Sancak B, Yildiz R, et al. Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer. Adv Ther. 2008;25(8):801–9.PubMedCrossRef
30.
Chang ST, Zahn JM, Horecka J, Kunz PL, Ford JM, Fisher GA, et al. Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis. J Transl Med. 2009;7:105.PubMedPubMedCentralCrossRef
31.
Høgdall EV, Ringsholt M, Høgdall CK, Christensen IJ, Johansen JS, Kjaer SK, et al. YKL-40 tissue expression and plasma levels in patients with ovarian cancer. BMC Cancer. 2009;9:8.PubMedPubMedCentralCrossRef
32.
Johansen JS, Bojesen SE, Mylin AK, Frikke-Schmidt R, Price PA, Nordestgaard BG. Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population. J Clin Oncol. 2009;27(4):572–8.PubMedCrossRef
33.
Mitsuhashi A, Matsui H, Usui H, Nagai Y, Tate S, Unno Y, et al. Serum YKL-40 as a marker for cervical adenocarcinoma. Ann Oncol. 2009;20(1):71–7.PubMedCrossRef
34.
Choi IK, Kim YH, Kim JS, Seo JH. High serum YKL-40 is a poor prognostic marker in patients with advanced non-small cell lung cancer. Acta Oncol. 2010;49(6):861–4.PubMedCrossRef
35.
Thöm I, Andritzky B, Schuch G, Burkholder I, Edler L, Johansen JS, et al. Elevated pretreatment serum concentration of YKL-40-An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer. Cancer. 2010;116(17):4114–21.PubMedCrossRef
36.
Iwamoto FM, Hottinger AF, Karimi S, Riedel E, Dantis J, Jahdi M, et al. Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas. Neuro Oncol. 2011;13(11):1244–51.PubMedPubMedCentralCrossRef
37.
Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, et al. Serum YKL-40 following resection for cerebral glioblastoma. J Neurooncol. 2012;107(2):299–305.PubMedCrossRef
38.
Wang D, Zhai B, Hu F, Liu C, Zhao J, Xu J. High YKL-40 serum concentration is correlated with prognosis of Chinese patients with breast cancer. PLoS ONE. 2012;7(12):e51127.PubMedPubMedCentralCrossRef
39.
Zhu CB, Wang C, Chen LL, Ma GL, Zhang SC, Su L, et al. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma. PLoS ONE. 2012;7(9):e44648.PubMedPubMedCentralCrossRef
40.
Zhu CB, Chen LL, Tian JJ, Su L, Wang C, Gai ZT, et al. Elevated serum YKL-40 level predicts poor prognosis in hepatocellular carcinoma after surgery. Ann Surg Oncol. 2012;19(3):817–25.PubMedCrossRef
41.
Schultz NA, Christensen IJ, Werner J, Giese N, Jensen BV, Larsen O, et al. Diagnostic and Prognostic impact of circulating YKL-40, IL-6, and CA 19.9 in patients with pancreatic cancer. PLoS ONE. 2013;8(6):e67059.PubMedPubMedCentralCrossRef
42.
Gállego Pérez-Larraya J, Paris S, Idbaih A, Dehais C, Laigle-Donadey F, Navarro S, et al. Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL-40 plasma levels in patients with glioblastoma. Cancer. 2014;120(24):3972–80.PubMedCrossRef
43.
Liu X, Zhang Y, Zhu Z, Ha M, Wang Y. Elevated pretreatment serum concentration of YKL-40: an independent prognostic biomarker for poor survival in patients with colorectal cancer. Med Oncol. 2014;31(8):85.PubMedCrossRef
44.
Tarpgaard LS, Guren TK, Glimelius B, Christensen IJ, Pfeiffer P, Kure EH, et al. Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study. PLoS ONE. 2014;9(2):e87746.PubMedPubMedCentralCrossRef
45.
Tschirdewahn S, Reis H, Niedworok C, Nyirady P, Szendröi A, Schmid KW, et al. Prognostic effect of serum and tissue YKL-40 levels in bladder cancer. Urol Oncol. 2014;32(5):663–9.PubMedCrossRef
46.
Xu CH, Yu LK, Hao KK. Serum YKL-40 level is associated with the chemotherapy response and prognosis of patients with small cell lung cancer. PLoS ONE. 2014;9(5):e96384.PubMedPubMedCentralCrossRef
47.
Jensen BV, Spindler KLG, Christensen IJ, Schou JV, Nielsen DL, Jakobsen A, Høgdall E, Pfeiffer P, Yilmaz MK, Johansen J. Plasma YKL-40 as a biomarker for poor prognosis in patients with metastatic colorectal cancer treated with 3. line cetuximab and irinotecan. Ann Oncol. 2016; 27(Supplement 6).
48.
Vom Dorp F, Tschirdewahn S, Niedworok C, Reis H, Krause H, Kempkensteffen C, et al. Circulating and tissue expression levels of YKL-40 in renal cell cancer. J Urol. 2016;195(4 Pt 1):1120–5.CrossRef
49.
Boisen MK, Madsen CV, Dehlendorff C, Jakobsen A, Johansen JS, Steffensen KD. The prognostic value of plasma YKL-40 in patients with chemotherapy-resistant ovarian cancer treated with bevacizumab. Int J Gynecol Cancer. 2016;26(8):1390–8.PubMedCrossRef
50.
Thongsom S, Chaocharoen W, Silsirivanit A, Wongkham S, Sripa B, Choe H, et al. YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma. Tumour Biol. 2016;37(7):9451–63.PubMedCrossRef
51.
Krogh M, Christensen I, Bouwhuis M, Johansen JS, Nørgaard P, Schmidt H, et al. Prognostic and predictive value of YKL-40 in stage IIB-III melanoma. Melanoma Res. 2016;26(4):367–76.PubMedCrossRef
52.
Gramkow MH, Peltonen R, Dehlendorff C, Osterlund PJ, Johansen JS, Isoniemi H. The prognostic value of serum IL-6 and YKL-40 in colorectal cancer patients before liver resection. J Clin Oncol. 2017;35(15 Supplement):1.
53.
Erturk K, Tas F, Serilmez M, Bilgin E, Yasasever V. Clinical significance of serum Ykl-40 (Chitinase-3-Like-1 Protein) as a biomarker in melanoma: an analysis of 112 Turkish patients. Asian Pac J Cancer Prev. 2017;18(5):1383–7.PubMedPubMedCentral
54.
Väänänen T, Kallio J, Vuolteenaho K, Ojala A, Luukkaala T, Hämäläinen M, et al. High YKL-40 is associated with poor survival in patients with renal cell carcinoma: a novel independent prognostic marker. Scand J Urol. 2017;51(5):367–72.PubMedCrossRef
55.
Fuksiewicz M, Kotowicz B, Rutkowski A, Achinger-Kawecka J, Wagrodzki M, Kowalska MM. The assessment of clinical usage and prognostic value of YKL-40 serum levels in patients with rectal cancer without distant metastasis. Technol Cancer Res Treat. 2018;17:1533033818765209.PubMedPubMedCentralCrossRef
56.
Darr C, Krafft U, Hadaschik B, Tschirdewahn S, Sevcenco S, Csizmarik A, et al. The role of YKL-40 in predicting resistance to docetaxel chemotherapy in prostate cancer. Urol Int. 2018;101(1):65–73.PubMedCrossRef
57.
Matsuo N, Azuma K, Hattori S, Ohtake J, Kawahara A, Ishii H, et al. Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti-PD-1 inhibitor. Int J Cancer. 2019;144(5):1170–9.PubMedCrossRef
58.
Jeet V, Tevz G, Lehman M, Hollier B, Nelson C. Elevated YKL40 is associated with advanced prostate cancer (PCa) and positively regulates invasion and migration of PCa cells. Endocr Relat Cancer. 2014;21(5):723–37.PubMedPubMedCentralCrossRef
59.
Pelloski CE, Ballman KV, Furth AF, Zhang L, Lin E, Sulman EP, et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol. 2007;25(16):2288–94.PubMedCrossRef
60.
Pelloski CE, Mahajan A, Maor M, Chang EL, Woo S, Gilbert M, et al. YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin Cancer Res. 2005;11(9):3326–34.PubMedCrossRef
61.
Shao R, Cao QJ, Arenas RB, Bigelow C, Bentley B, Yan W. Breast cancer expression of YKL-40 correlates with tumour grade, poor differentiation, and other cancer markers. Br J Cancer. 2011;105(8):1203–9.PubMedPubMedCentralCrossRef
62.
Kang EJ, Jung H, Woo OH, Park KH, Woo SU, Yang DS, et al. YKL-40 expression could be a poor prognostic marker in the breast cancer tissue. Tumour Biol. 2014;35(1):277–86.PubMedCrossRef
63.
Bojesen SE, Johansen JS, Nordestgaard BG. Plasma YKL-40 levels in healthy subjects from the general population. Clin Chim Acta. 2011;412(9–10):709–12.PubMedCrossRef
Metadata
Title
Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies
Authors
Bingxian Bian
Li Li
Junyao Yang
Yi Liu
Guohua Xie
Yingxia Zheng
Liang Zeng
Junxiang Zeng
Lisong Shen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0983-y

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

Protective potential of miR-146a-5p and its underlying molecular mechanism in diverse cancers: a comprehensive meta-analysis and bioinformatics analysis

Review

Effects of pericytes and colon cancer stem cells in the tumor microenvironment

Primary research

Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Primary research

Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer

Primary research

Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma

Primary research

A nomogram based on 9-lncRNAs signature for improving prognostic prediction of clear cell renal cell carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits